Device for stirring samples

Abstract

The invention relates to a device for shaking samples, comprising a carrier (62) and a drive element (66) rotatably mounted on the carrier (62) around a drive axis and drivable by a drive (65). The device further comprises a tray (61) arranged to load samples (69), a tray shaft (67) connected to the tray (61) and eccentrically mounted on the drive element (66), and a counterweight (66a) attached to the drive element (66) and adapted to compensate for an imbalance caused during operation of the device by a predetermined load on the tray (61). The center of gravity of the counterweight (66a) is located on the opposite side of the tray shaft (67) with respect to the drive axis of the drive element (66). The center of gravity of the counterweight (66a) and the center of gravity of the tray (61), together with the tray shaft (67) and the predetermined load, are in the same plane perpendicular to the drive axis. When the drive element (66) rotates about the drive shaft, a first torque exerted on the drive shaft by the tray shaft (67) and the tray (61) together with a given load is equal in magnitude and directed opposite to a second torque exerted on the drive shaft by the counterweight (66a). As a result, the counterweight (66a) is adapted to compensate both static and dynamic imbalances on the drive shaft. Thus, the vibration frequency of the tray (61) by the drive (65) reaches at least 1000 rpm, in particular at least 2000 rpm.

Description

[Technical field]

[0001] The present invention relates to a device for shaking a sample, in particular for shaking and / or mixing a sample containing a liquid, in particular a laboratory shaker. The present invention is advantageous for the cultivation of bacteria and cells in liquid media. [Background technology]

[0002] Shakers are used to shake and / or mix liquids in containers, such as cell cultures, biofuels or blood samples, with an orbital motion. Shaking units often comprise a tray in which the containers with the samples, such as Erlenmeyer flasks, test tubes or other ampoules, are located. For good mixing, a high shaking frequency is desirable. At the same time, a high shaking frequency allows for a fast oxygen transfer from the gas phase to the liquid phase, facilitating good growth of the cell cultures.

[0003] However, especially at high shaking frequencies, considerable unbalances of the rotating components occur during the shaking process, for example on the drive shaft and / or drive element to which the tray is mounted. Such unbalances lead to vibrations of the shaker during the shaking process, and therefore noise, and damaging forces on the bearings to which the rotating components are mounted, which in turn leads to increased wear. In this respect, the unbalances of the rotating components limit the maximum shaking frequency that can be practically achieved for the continuous operation of the shaker. As a result, the cultivation of cells in a conventional shaker allows much slower growth and significantly less biomass production than the cultivation in a bioreactor.

[0004] EP 3479894 A1 presents an agitator in which a tray with a tray shaft is eccentrically mounted in a drivable hollow shaft. The hollow shaft is provided with a counterweight to balance the imbalance caused by the eccentric mass distribution. However, this counterweight (17 in FIG. 2) has the disadvantage that it only partially compensates for the imbalance of the hollow shaft, in particular because it only compensates for the static imbalance.

[0005] The problem is therefore to provide an apparatus for shaking samples that allows better mixing of the samples and / or sufficiently good mixing of larger samples. Alternatively, the problem can be seen in providing an apparatus for shaking samples that is suitable for continuous operation at high shaking frequencies of more than 1000 rpm, in particular more than 1500 rpm, 2000 rpm or 2500 rpm, for example with an orbital motion diameter of 3 mm. Summary of the Invention

[0006] This problem is solved by a device for shaking samples, a so-called shaker, according to claim 1. By sample is meant in particular a substance or composition of matter containing a liquid, for example a cell culture, a biofuel or a blood sample. The sample is usually contained in a container, for example a test tube or a microtiter plate, which can then be held by a container holder or a stand.

[0007] The apparatus comprises: - Carrier: The carrier is specifically designed to carry or support the tray. - a drive element which is journalled to the carrier and can thus rotate about a drive axis and which can be driven by a drive, for example by a motor: the drive element can for example comprise a hollow shaft or a drive disk. - Tray for loading samples: in particular, the tray is a surface element on which the samples can be mounted. Advantageously, the tray comprises fastening elements for fastening at least one container with the sample or for fastening at least one container holder or stand. - A tray shaft connected to the tray, in particular rigidly connected and eccentrically journalled on the drive element: Advantageously, the tray shaft is attached in the centre of the tray, in particular close to the centre of gravity of the tray or the centre of gravity of the tray with a given load of samples. The term "close" refers in particular to the area around the centre of gravity up to + / - 10% of the length and width of the tray. By means of a central attachment, the tray shaft (with a given load) supports the tray close to the centre of gravity.

[0008] The eccentricity (of the bearing) of the tray shaft on the drive element is in particular the distance between the rotation axis of the tray shaft and the drive axis of the drive element, which run parallel to each other. The eccentricity determines the deflection of the tray (and therefore the sample) during shaking. In particular, the eccentricity of the bearing of the tray shaft on the drive element may be 0.5-3 mm, in particular 1-2 mm. This results in a deflection of the tray suitable for shaking samples in smaller vessels, e.g. test tubes and microtiter plates.

[0009] The shaking frequency that the tray can achieve as a result of the drive is at least 1000 rpm, in particular at least 1500 rpm, at least 2000 rpm or at least 2500 rpm. This high shaking frequency cannot be achieved with previous shakers, in particular due to mismatch. A shaking frequency in this range results in good mixing of the samples, in particular in smaller vessels, such as test tubes and microtiter plates, in particular in vessels with a volume of up to 1 ml. Furthermore, with a shaking frequency in this range, sufficient mixing of larger samples, in particular with a volume of more than 1 ml, for example 2 ml, can also be achieved, which is not possible with lower shaking frequencies. The shaking device according to the invention can therefore be used to culture larger quantities of cells, for example in taller vessels, which makes the culture significantly more efficient.

[0010] Furthermore, the device comprises a counterweight attached to the drive element, which is adapted to compensate for the imbalance caused by the predetermined load on the tray during operation of the device. The predetermined load of the tray with samples is characterized in particular by the mass, e.g. the number of samples x the average mass of the samples + the mass of the containers and any container holders, and the mass distribution on the tray, e.g. the distribution or center of gravity of the samples, containers and any container holders on the tray. In order to compensate for the imbalance well, the mass and the mass distribution or center of gravity of the load preferably deviate only slightly from the predetermined value, i.e. the predetermined load. In terms of the mass, this means in particular a deviation of up to + / - 25% in terms of the center of gravity, in particular a deviation of up to 3 cm.

[0011] Unbalance is specifically defined as a rotating body whose axis of rotation does not correspond to one of its principal axes of inertia. Static unbalance occurs specifically when the axis of rotation does not pass through the center of gravity of the body. Dynamic unbalance (also known as moment unbalance) occurs when the axis of rotation does not coincide with one of the principal axes of inertia of the body, but is inclined to the principal axes of inertia at the center of gravity. In general, an object with any axis of rotation exhibits both static and dynamic unbalance. Unbalance can be clearly decomposed into static and dynamic components. The static component results in a rotational resultant force, while the dynamic component results in a rotational resultant torque. Both the resultant force and the resultant torque increase quadratically with speed.

[0012] According to the invention, the counterweight is adapted to compensate both static and dynamic imbalance on the drive shaft. Advantageously, the counterweight is the only counterweight on the drive element. In particular, there is no further counterweight on the side of the drive element opposite the tray. This is different from conventional imbalance compensation in shakers: conventionally, one counterweight is used only to compensate static imbalance, while another counterweight is needed to compensate dynamic imbalance.

[0013] An apparatus with a counterweight that compensates for both static and dynamic unbalance on the drive shaft has several advantages: on the one hand, it is possible to avoid a resultant torque on the drive shaft, especially on its bearings. This leads to less noise emissions and less wear, especially at high shaking frequencies (especially above 1000 rpm), and therefore to a longer life of the apparatus. On the other hand, the apparatus can be built compactly with a (single) counterweight, which is particularly advantageous for shakers with several trays stacked on top of each other. Furthermore, high shaking frequencies, especially above 1000, 1500, 2000 or 2500 rpm, can only be achieved with the described counterweights. This leads to better mixing of the sample being shaken and faster oxygen transfer from the gas phase to the liquid phase, which allows better growth of cell cultures in the sample.

[0014] Counterweight To compensate for static and dynamic imbalance, the center of gravity of the counterweight is located on the opposite side of the tray shaft with respect to the drive shaft of the drive element. Because the weight of the tray and its load act eccentrically on the drive element through the tray shaft, the counterweight is attached to the drive element such that the center of gravity of the counterweight is on the opposite side of the tray shaft with respect to the drive shaft. In particular, when the drive element rotates, the center of gravity of the counterweight and the tray shaft rotate around the drive shaft. By proper selection of the mass and center of gravity of the counterweight, the static imbalance can be compensated for.

[0015] Additionally, the center of gravity of the counterweight and the center of gravity of the tray, along with the tray shaft and the specified load, are in the same plane perpendicular to the drive shaft, thereby reducing the occurrence of dynamic imbalance.

[0016] Furthermore, as the drive element rotates about the drive axis, a first torque exerted on the drive axis by the tray in conjunction with the tray shaft and the predetermined load is equal in magnitude to and opposite in direction to a second torque exerted on the drive axis by the counterweight. In this manner, static and dynamic imbalance on the drive element can be avoided.

[0017] In one embodiment, the tray has a protrusion in the area of ​​the tray shaft, in which the counterweight is at least partially located. In particular, the center of gravity of the counterweight is located inside the protrusion. This has the advantage that the counterweight as well as other components, such as the tray shaft and the drive elements, are protected from contamination by the tray, for example from spilled or splashed samples. This makes it easier to clean the device after contamination. At the same time, the specific arrangement of the protrusion and the counterweight can ensure that the center of gravity of the counterweight and the center of gravity of the tray are in the same plane with the tray shaft and a given load (as described above).

[0018] Advantageously, the counterweight has a mass of 0.1-1 kg, in particular 0.5-0.9 kg. Furthermore, the counterweight can be made of metal, in particular cast iron or stainless steel. Due to its high density, such a counterweight can be dimensioned compactly and fit into protrusions to save space. Furthermore, such a counterweight only needs to be mounted at a distance of a few centimetres, in particular 1-5 cm, for example 2-3 cm, from the drive shaft in order to compensate for the above-mentioned advantageous eccentricities of, for example, 0.5-3 mm, in particular 1-2 mm, and for example the imbalance due to the load on the tray of 15, 20 or 25 kg.

[0019] In one embodiment, the tray has a rectangular shape. This allows space-saving loading of the tray with typical vessels and vessel holders. In particular, the tray can have a length of 50-100 cm and / or a width of 30-70 cm. Such a tray is suitable both for table shakers, which are arranged as independent devices, for example on a laboratory bench, and for multi-shakers, which consist of several trays stacked on top of each other, for example enclosed in a housing.

[0020] Tray rotation lock Advantageously, the tray is fixed against rotation relative to the carrier to generate the desired orbital motion; otherwise, the tray would also rotate about the drive shaft as the drive element rotates. However, for the shaking process, it is desirable to have an orbital motion, imparted in particular by the eccentricity of the bearing of the tray shaft on the drive element, i.e. to translate the tray together with the load on a circular path. Such translation can be achieved in various ways.

[0021] In one embodiment, the drive element has a first belt pulley for driving via a belt. Furthermore, the device comprises a second drive element and a second tray shaft connected to the tray and eccentrically journalled to the second drive element. The second drive element also has a counterweight attached thereto for compensating the imbalance, as described above. In particular, the center of gravity of the second counterweight is located on the opposite side of the second tray shaft with respect to the second drive axis of the second drive element. Furthermore, the center of gravity of the second counterweight and the center of gravity of the tray, together with the second tray shaft and the predetermined load, are located in the same plane extending perpendicular to the second drive axis. Furthermore, when the second drive element rotates around the second drive axis, a third torque exerted by the tray together with the second tray shaft and the predetermined load on the second drive axis is equal in magnitude to and directed in the opposite direction to a fourth torque exerted by the second counterweight on the second drive axis. Advantageously, the second drive element comprises a second belt pulley connected to the first belt pulley via a toothed belt and thus driven. Advantageously, the tray is journalled to the second drive element with the same eccentricity as the drive element together with the first belt pulley, whereby the tray is fixed against rotation by the synchronous drive of the first and second belt pulleys.

[0022] In a particularly advantageous embodiment comprising a first and a second belt pulley, a first and a second tray shaft and a first and a second drive element, the tray comprises a first and a second tray part. The first and the second tray shaft are in particular rigidly connected to the first and the second tray part and eccentrically journalled to the first and the second drive element. To prevent rotation of the tray, the first and the second tray part are connected to each other by a linear guide. Such a linear guide is in particular designed to ensure that the first and the second tray part can move relative to each other along the axis of the linear guide but cannot rotate relative to each other. In other words, the linear guide limits all degrees of freedom of the tray parts relative to each other, except for the translational degree of freedom along the axis of the linear guide. The embodiment having two tray sections connected by a linear guide has the advantage that damaging forces on the tray shaft bearings caused, for example, by thermal expansion of the integral tray are prevented, allowing for higher shaking frequencies, longer operating times, and smoother shaker operation.

[0023] Alternatively, rotation of the tray may be prevented by a device further comprising flexible and / or articulating elements attached to the carrier or to a housing connected to the carrier and designed to guide the tray. Advantageously, the flexible and / or articulating elements engage in edge regions of the tray.

[0024] housing In one embodiment, the device further comprises an openable housing, the tray, the tray shaft, the drive element and the carrier being located in an interior space within the housing. On the one hand, the housing can serve to seal the tray and the sample from the environment of the device, for example to prevent contamination of the environment by splashing liquids. On the other hand, the housing can be designed to air condition the interior. For this purpose, the device can comprise a climate control element that is set to control the temperature and / or humidity inside the housing. For this purpose, in particular to create ideal ambient conditions for the samples, the climate control element can comprise, for example, a heater, a cooler, a humidifier and / or a dehumidifier that can be attached to the housing. In order to openably close the housing and thus maintain the ideal ambient conditions, the housing advantageously comprises a door, for example a hinged door, in particular at the front of the housing.

[0025] Several trays In one embodiment, the device comprises at least one further tray with a further tray shaft, a further drive element, a further counterweight and a further carrier inside the housing. In particular, the device can comprise at least five further trays with a further tray shaft, a further drive element, a further counterweight and a further carrier inside the housing. This increases the capacity of the device, i.e. in particular the number of samples that can be shaken simultaneously. Advantageously, the drive element and the at least one further drive element or the at least five further drive elements can be driven via a main drive shaft. The common drive via the main drive shaft results in an easy-to-maintain and compact design.

[0026] To avoid imbalance in the case of several trays, it is advantageous for the angular position of the bearing of the additional tray shaft on the additional drive element to be offset from the angular position of the bearing of the tray shaft on the drive element, which would otherwise act on the main drive shaft and cause the whole device to vibrate, especially in the case of heavy tray loads.

[0027] This can be avoided in particular if the angular positions of the bearings of the various tray shafts differ from each other by 360° / N, where N is the number of trays in the machine, thereby compensating for any imbalances on the main drive shaft.

[0028] Drive unit In one embodiment, the drive comprises a motor, e.g. an electric motor, for driving the drive element and, if present, at least one further drive element. In particular, the motor can be coupled to the main drive shaft via a gearbox.

[0029] Advantageously, the motor is mounted outside the housing, if a housing is present. Mounting the motor outside the housing has the advantage that heat generated during operation of the motor is not introduced into the interior of the housing. For many applications or samples, it is desirable to control the temperature and / or humidity, for example by a climate control as described above. In particular, the humidity is kept close to the dew point, in particular with a relative humidity of 80% to 100%. However, if the interior has to be cooled at the same time, for example because of heat input from an engine inside, the humidity may reach 100% locally at the climate control or radiator and condense. Condensation is again undesirable, since it may result in uncontrolled growth of foreign bacteria that may be harmful to the sample. In particular, the interior of the housing should be thermally isolated from the motor. This problem is solved by a motor mounted outside the housing.

[0030] In particular, the motor can be mounted on the underside of the housing. This lowers the centre of gravity of the device and therefore increases its stability, especially at high vibration frequencies. The main drive shaft is advantageously guided through an opening in the underside of the housing.

[0031] It should be noted that the various embodiments may also be combined where technically feasible, thereby achieving synergies and further advantages.

[0032] Further embodiments, advantages and applications of the invention are evident from the dependent claims and the following description with reference to the drawings. [Brief description of the drawings]

[0033] [Figure 1a] FIG. 1 is a perspective view of an apparatus for shaking a sample according to one embodiment of the present invention. [Figure 1b] FIG. 1b is a top view of the device of FIG. [Diagram 2] FIG. 1 is a schematic cross-sectional view of an apparatus for shaking samples using an internal motor according to the state of the art. [Diagram 3] FIG. 1 is a schematic cross-sectional view of an apparatus for shaking a sample using an external motor according to one embodiment of the present invention. [Figure 4] FIG. 1 is a schematic side view of one embodiment of an apparatus according to the invention having several trays. [Figure 5a] FIG. 1 is a schematic diagram of a device for shaking samples according to the state of the art with compensation for static imbalance. [Figure 5b] FIG. 1 is a schematic diagram of a device in which both static and dynamic imbalance are compensated. [Figure 6a] 1 is a schematic cross-sectional side view of an apparatus for shaking a sample according to one embodiment; [Figure 6b] FIG. 6b is a detailed view of area C of FIG. 6a. [Figure 7] FIG. 2 is a horizontal cross-sectional or top view of a tray and counterweight according to one embodiment of the present invention. [Figure 8a] FIG. 1 is a schematic diagram of a liquid sample in a container with increasing shaking frequency. [Figure 8b] FIG. 1 is a schematic diagram of a liquid sample in a container with increasing shaking frequency. [Figure 8c] FIG. 1 is a schematic diagram of a liquid sample in a container with increasing shaking frequency. [Figure 9] FIG. 2 is a schematic cross-sectional view of a bearing with a tray journalled to a main drive shaft according to one embodiment. [Figure 10a] FIG. 1 illustrates a perspective view of a pivoting tray having a latch mechanism according to one embodiment. [Figure 10b] FIG. 10b is a close-up view of the latch mechanism of FIG. [Figure 11a] FIG. 1 is a perspective view of an embodiment having a dividing tray. [Figure 11b] FIG. 2 is a schematic horizontal cross-sectional view of an embodiment having a dividing tray. [Figure 11c] FIG. 2 is a schematic side cross-sectional view of an embodiment having a dividing tray. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0034] Figures 1a and 1b show an apparatus for shaking samples, a so-called shaker, according to one embodiment. Figure 1a shows a perspective view of the apparatus, and Figure 1b shows a top view. The apparatus comprises a tray 11 designed to be loaded with samples. The tray 11 is supported pivotally on a carrier 12 (not visible in Figures 1a and 1b). The carrier 12 and thereby the tray 11 can pivot around a main drive shaft 13. For this purpose, the carrier 12 is connected to the main drive shaft 13 via a bearing 13a, for example a ball bearing. Furthermore, the tray 11 has in its edge region an opening 11a through which the main drive shaft 13 passes. The opening 11a is larger than the diameter of the main drive shaft 13, depending on the eccentricity of the tray's bearing, in particular the deflection of the shaking movement.

[0035] The tray 11 advantageously comprises at least on its upper side, i.e. the side facing the samples, an easily cleanable, e.g. metallic, surface, which allows a sterile operation of the device. Furthermore, the tray 11 can have a standard size of 850 mm x 470 mm.

[0036] The tray 11 in the folded state 11' and at least a part of the main drive shaft 13 can be enclosed by a housing 14 with a door 14a for opening and closing. The housing 14 generally performs several functions: firstly, it forms a fixed frame that can be placed on a table, in a laboratory or generally on a base, for example via legs 14b. The shaking movement of the tray is performed relative to this fixed frame. Secondly, the housing provides protection of the environment of the device from splashes or spills or steam of samples, which is particularly desirable, for example, in harmful samples or in sterile laboratories. Thirdly, controlled conditions, for example in terms of temperature and / or humidity, can be set inside the housing, as is advantageous for many samples. For this purpose, the device may be equipped with a climate control for the interior (not shown in Figures 1a and 1b, as mentioned above).

[0037] In Figures 1a and 1b the tray is shown in two positions, on the one hand (reference number 11) swung out of the housing 14 and on the other hand (dashed line, reference number 11') swung in the operating state into the housing. In the figures the angle between the two positions is 90°. However, in general an angle of at least 45° is already advantageous as it improves the accessibility of the tray 11 and the interior of the housing 14.

[0038] Moreover, in Fig. 1a and Fig. 1b it can be seen that the mounting of the main drive shaft 13 in the edge region or even in the corner region of the tray, in particular less than 20% of the tray's length and / or width away from the tray's edge, is advantageous for the pivotability and accessibility of the tray. Alternatively, the same advantage can be achieved by the main drive shaft 13 extending outside the tray 11 close to its edge region, in particular less than 20% of the tray's length or width away from the tray's edge (not shown in Fig. 1a and Fig. 1b). In this case, the opening 11a in the tray 11 is unnecessary and the carrier 12 protrudes horizontally beyond the tray 11. In general, the pivotability of the tray from the housing improves the accessibility of the samples. In particular, a pivoting tray allows the automation of the sample filling and removal process, since for example a robotic arm can operate the device more easily under computer control.

[0039] Figure 2 is a schematic cross-sectional view of a shaker according to the state of the art. The tray 21 is driven by a motor 25 located inside the housing 24. Placing the motor 25 inside the housing 24 has the disadvantage that the heat generated by the motor 25 directly heats the interior and thus the samples located inside. However, for some samples, it is necessary to air-condition the interior, in particular to control the temperature and / or humidity, for example via the air-conditioning control 26. As mentioned above, this can cause condensation of moisture inside, in particular in the air-conditioning control 26 or in a cooler, which can in turn damage the samples. The internal motor 25 contributes to this problem, since the heat generated by the motor 25 must be removed from the interior by the air-conditioning control 26.

[0040] Figure 3 shows a further embodiment of the invention with a schematic cross-section of the shaker. In contrast to Figure 2 (prior art), the tray 31 can here be driven via a main drive shaft 33 by a motor 35 mounted outside the housing 34. The main drive shaft 33 extends orthogonally to the tray 31 into most of the interior of the housing 34, a smaller part of the main drive shaft 33 extending outside the housing. The positioning of the motor 35 below the housing 34 is advantageous with regard to a low centre of gravity of the device.

[0041] In particular, a motor mounted outside the housing as in Fig. 3 generally has the advantage that the heat generated by the motor is not introduced into the interior of the housing and therefore does not heat up the housing. This means that less cooling power is needed to keep the interior at a constant temperature. As a consequence, less moisture condenses locally inside, for example in the climate control unit or cooler, which could be harmful to the specimen. This makes it easier to create controlled environmental conditions inside, in particular constant temperature and high humidity, for example 80% to 100% relative humidity, without condensation.

[0042] Figure 4 shows a shaker with several, in particular six, trays 41, drivable by a single main drive shaft 43, in a housing 44 with a door 44a. All the trays 41 can therefore be driven by a motor (not shown in Figure 4), which, as mentioned above, can be mounted outside the possibly conditioned interior of the housing 44. Advantageously, the main drive shaft 43 again extends through the trays 41 in the edge regions, in particular in the corner regions, for optimal pivoting of the trays 41.

[0043] FIG. 5a shows by way of a schematic diagram how the static unbalance of a conventional shaker (as described in the "Background Art" section above) can be compensated. A tray 51 with a load 59, e.g. with samples, vessels and vessel holders, is eccentrically journalled to a drive element, e.g. a hollow shaft, via a tray shaft 57. The bearing 57a of the tray shaft 57 on the drive element is not on the drive shaft 52b about which the drive element rotates due to its bearing 52a on the carrier 52. Rather, the bearing 57a is spaced from the drive shaft 52b by a first radius r1 due to the eccentricity. The mass of the tray 51, the load 59 and the tray shaft 57 thus represent an unbalance mass u1, which results in an unbalance U1=u1×r1.

[0044] According to the prior art, the counterweight 56a is attached to the drive element to compensate for the static unbalance U1, so that the center of gravity SP2 of the counterweight 56a is opposite to the center of gravity SP1 of the unbalance mass u1 with respect to the drive shaft 52b. In this case, the counterweight 56a is attached, for example, in the direction of the drive shaft 52b between the center of gravity SP1 and the bearing 52a of the drive element. If the unbalance U2=u2×r2 of the counterweight 56a with the mass u2 of the counterweight and the distance r2 of the center of gravity SP2 from the drive shaft 52b is the same size as the unbalance U1=U2, the static unbalance is just compensated. In other words, if the drive shaft 52b is horizontal, the drive element will not rotate from any initial position without the influence of an external force.

[0045] However, the arrangement with counterweight 56a according to Figure 5a still has a dynamic imbalance because the imbalances U1 and U2 are offset from each other by a center distance 1 in the direction of the drive shaft 52b. When the drive elements (including the tray 51, the load 59, the tray shaft 57, and the counterweight 56a) rotate, the force F1 = U1 x ω 2 and F2 = U2 × ω 2acts on the drive shaft 52b (see the thick arrow in FIG. 5a), where ω is the angular frequency. Since U=U1=U2, and F=F1=-F2 for opposing forces F1 and F2, these forces result in a torque M that is perpendicular to the drive shaft 52b and rotates with it: M=F1×l / 2-F2×l / 2=l×F=l×U×ω 2 This results in a deviation torque D = u x l x r = U x l if the static imbalance is ideally balanced.

[0046] Fig. 5b shows a schematic diagram of how the dynamic imbalance can be compensated by an additional counterweight 56b. For this purpose, the additional counterweight 56b, together with the load 59 and the tray shaft 57 as well as the counterweight 56a, is mounted on the other side of the bearing 52a, like the tray 51, in the direction of the drive shaft 52b. Furthermore, the additional counterweight 56b, having a mass u3, a center of gravity SP3 and a center distance r3 of the center of gravity SP3 to the drive shaft 52b, is mounted on the same side as the center of gravity SP1, i.e. opposite to the center of gravity SP2. As a result, an additional force F3 acts during rotation about the drive shaft, similarly to the above.

[0047] Thus, by suitable selection of u3 and r3, in addition to the static unbalance, the dynamic unbalance on the drive shaft 52b can be compensated, thereby preventing damaging forces and wear on the bearing 52a. However, a drawback of the arrangement according to Fig. 5b is the need to provide two counterweights 56a and 56b, which prevents a space-saving design.

[0048] Therefore, one aspect of the invention relates to a space saving arrangement of counterweights that compensates for both static and dynamic imbalance. Such an arrangement is described below with reference to Figure 6b.

[0049] Figures 6a and 6b focus on the mechanical aspects of how the tray 61 is pivotally mounted on the main drive shaft 63 via a carrier 62 with bearings 63a (Figure 6a) and on the details of the drive of the tray 61 via a drive element 66 with counterweight 66a (Figure 6b). In principle, the described mechanism can also be applied to several trays, for example the shaker according to Figure 4.

[0050] The tray 61 is set up to be loaded with one or more samples 69 to be shaken, for example in a microtiter plate. For this purpose, the tray 61 preferably has fastening elements, for example for a vessel stand, to hold the sample 69 or vessel, in particular a microtiter plate, stationary relative to the tray 61 during the shaking process.

[0051] The tray 61 is rotatably mounted to the drive element 66 via a fixed tray shaft 67. The drive element 66 is in turn rotatably mounted to a carrier 62, which is pivotally mounted to the main drive shaft 63 via bearing 63a. The bearing of the tray shaft 67 in or on the drive element 66 is eccentric so that the axis of rotation of the tray shaft 67 does not coincide with the axis of rotation of the drive element 66. This eccentricity of the tray shaft 67 results in a circular motion in which the tray 61 rotates when the drive element 66 rotates, thus resulting in the desired shaking of the tray 61 together with the sample 69.

[0052] Optionally, tray 61 is surrounded as it pivots by housing 64, which serves to protect against splashing and / or condition the samples as described above. A main drive shaft 63 extends through housing 64, particularly vertically, i.e., in the direction of gravity, and is rotatably mounted to housing 64. Additionally, a motor 65 for driving main drive shaft 63 is attached, preferably externally, to housing 64.

[0053] Additionally, the housing 64 (as previously described with reference to FIG. 1a) may include legs 64b adapted to support the weight of the device. In general, the legs may also be adapted for attachment to a support such as a laboratory bench.

[0054] FIG. 6b is an enlarged view of section C of FIG. 6a. The tray 61, which can be loaded with samples 69, for example in microtiter plates, is rotatably mounted on the drive element 66 via a tray shaft 67. The drive element 66 preferably comprises a belt pulley which is driven by the main drive shaft via a belt 68. For this purpose, a second belt pulley is attached to the main drive shaft and the belt 68 is tensioned across the two belt pulleys. Advantageously, the tray 61 is also eccentrically mounted on the second belt pulley, as well as the first belt pulley on the drive element 66. This provides an anti-rotation lock for the tray, since the freedom of movement of the tray 71 is limited to a circular translation. Furthermore, as mentioned above, the anti-rotation tray can comprise two tray parts connected to each other, for example by a linear guide.

[0055] It is generally advantageous to compensate for imbalances occurring in the rotating components of the apparatus (as discussed above). In addition to the main drive shaft, and see above in the section "Multiple Trays", this applies in particular to drive element 66. Particularly at high vibration frequencies and thus speeds such as those that the apparatus may reach, e.g., greater than 1000 rpm, greater than 1500 rpm, or greater than 2000 rpm, the imbalances would otherwise result in vibrations, increased wear on bearings and mountings, and excessive noise generation.

[0056] 6b shows an arrangement of a counterweight 66a on the drive element 66, which provides a particularly simple and effective compensation for the imbalance caused by the eccentric mounting of the tray 61 (with the specimen 69 and the tray shaft 67) on the drive element 66. The centre of gravity SP2 of the counterweight 66a lies in the same plane, perpendicular to the axis of rotation of the drive element 66, as the centre of gravity SP1 of the tray 61 together with the intended load of the specimen 69 and the tray shaft 67.

[0057] In general, the following applies: the two centres of gravity SP1 and SP2 are in the same plane perpendicular to the axis of rotation of the drive element 66, so the centre distance l=0 defined above (for FIG. 5a). The two forces F1 and F2 arising during rotation about the axis of rotation therefore act on the axis of rotation at the same point. This means that there are no deviation moments (D=U×l=0) and the occurrence of dynamic unbalance is prevented by design. The conditions for compensating for static unbalance (mentioned above for FIG. 5a) are also met, i.e. if U1=U2, this is also avoided.

[0058] To actually correct the unbalance, the above condition is considered to be fulfilled in particular if the unbalance U1 of the tray 61 together with the load 69 and the tray shaft 67 on the one hand, and the unbalance U2 of the counterweight 66a on the other hand, deviate from each other by a maximum of 25%. With regard to the centre distance l, i.e. the distance between the centres of gravity SP1 and SP2 in the direction of the axis of rotation, the above condition is considered to be fulfilled in particular if the centre distance l is a maximum of 1 cm. These tolerances make it possible to actually fully compensate the unbalance of the drive element 66 even in the case of small deviations from the given load, for example in terms of mass or mass distribution.

[0059] According to FIG. 6b, this can be solved in that the tray 61 is provided with an upward projection 61a under which at least part of the counterweight 66a is located. The torques exerted by SP1 and SP2 when the drive element 66 rotates about the axis of rotation generally only have to cancel each other out. With the illustrated arrangement, both static and dynamic unbalances can be compensated. This makes it possible to achieve high shaking frequencies of more than 1000 rpm, in particular more than 1500 rpm or even more than 2000 rpm, in a space-saving design. At the same time, this allows a long life and continuous operation of the shaker by avoiding increased wear.

[0060] FIG. 7 shows a top view or horizontal section of a tray 91 with a counterweight 96a. Two microtiter plates with a plurality of samples 99 are mounted on the tray 91, for example by means of a vessel holder. As described above in connection with FIG. 6b, the counterweight 96a is attached to the drive element 96, so that the imbalance caused by the eccentric mounting of the tray 91 (with samples 99) on the drive element 96 is compensated in a particularly simple and effective way. As shown, the counterweight 96a can be attached to the drive element 96, for example by means of a screw. Here too, the center of gravity of the counterweight 96a lies in the same plane as the center of gravity of the tray 91 together with the intended load of samples 99, perpendicular to the axis of rotation of the drive element 96.

[0061] Advantageously, the counterweight 96a is provided with an opening through which the tray shaft 97 extends. Furthermore, the counterweight 96a may advantageously be shaped similarly to a sector of a circle when viewed from above. Both embodiments allow for the largest possible volume, and therefore the largest possible mass, of the counterweight 96a, which nevertheless can rotate together with the drive element 96 within the protruding portion of the tray 91. This maximizes the space available for the specimens 99 on the tray 91.

[0062] Figures 8a, 8b and 8c show the effect of different shaking frequencies n1, n2 and n3 on a liquid sample in a container, such as a test tube or a microtiter plate. The sample volume V is the same in each figure: V1 = V2 = V3.

[0063] In Figure 8a, the sample is at rest, i.e. the shaking frequency n1 = 0. The sample liquid has an approximately flat horizontal surface. It fills the container to a height H1. This height can be considered as a measure of the diffusion distance d1 that oxygen must travel from the surrounding gas into the sample: d1 = H1.

[0064] In Figure 8b, the sample is oscillated at an oscillation frequency n2 > 0, for example n2 = 1000 rpm. The liquid is pressed upward at the edge of the container, and a meniscus, i.e., a concave surface of the sample liquid, is formed. While the surface area becomes larger compared to the situation in Figure 8a, the diffusion distance d2 = H2 - h2 decreases, and d2 < d1. As a result, oxygen enters the sample more rapidly in both cases.

[0065] In Figure 8c, the sample is oscillated much faster (n3 > n2), for example n3 = 2000 rpm. The sample liquid is "pulled" high up to the edge of the container. Due to the increase in the meniscus, the surface area further increases, the diffusion distance d3 = H3 - h3 further decreases, and d3 < d2. Therefore, the oxygen transport to the sample is further improved.

[0066] This demonstrates one of the main advantages of the described device that can achieve oscillation frequencies above 1000 rpm, especially above 1500 rpm or above 2000 rpm: the oxygen transport from the gas phase to the liquid phase, i.e., to the sample, is significantly increased. In particular, cells can be cultured at a rapid growth rate similar to that when cultured in a bioreactor and can produce a similar amount of biomass. Therefore, such a device can be used to conduct initial tests during cell culture under conditions similar to those used later in a bioreactor, especially during the maturation process.

[0067] Furthermore, Figures 8a, 8b, and 8c show that higher containers can be used at higher oscillation frequencies, and correspondingly, larger sample volumes can be sufficiently mixed. This means that the sample volume can be increased to at least twice, for example, from 1 ml to 2 ml per individual sample in a deep well plate, and the sample can still be sufficiently mixed to supply oxygen. This significantly shortens the time for cell culture and improves productivity.

[0068] FIG. 9 shows how the tray 71 can be journalled to the main drive shaft 73 via a carrier 72. Such a mounting is compatible with the embodiments of, for example, FIGS. 1a / 1b, 3, 4 and 6a / 6b. As in FIG. 6a / 6b, the tray 71 is journalled eccentrically on a drive element (not shown) having a first belt pulley. The drive element or first belt pulley is journalled rotatably on the support 72 and arranged to be driven via a belt 78. The belt 78 runs on a second belt pulley 75 which is also attached to the main drive shaft 73 and thus driven by a drive or motor via the main drive shaft 73.

[0069] A carrier 72 designed to support the weight of the tray 71 together with the sample load is journalled to the main drive shaft 73 via a bearing 73a, e.g. a ball bearing. In this way the carrier 72 can remain stationary while the main drive shaft 73 rotates, e.g. by being locked via a latch as in Fig. 10a / 10b. Preferably the bearing 73a is located below the second belt pulley 75.

[0070] Optionally, the carrier 72 together with the tray 71 may alternatively or additionally be journalled above the second belt pulley 75 via an additional bearing 73b on the main drive shaft 73. In general, care must be taken to ensure that the tray has sufficient clearance for the circular translation caused by the eccentric bearing. In particular, in a preferred embodiment, the opening in the tray 71 through which the main drive shaft 73 passes must be larger than the diameter of the main drive shaft 73 or the second bearing 73b, if present, by at least the eccentricity of the bearing.

[0071] Several carriers can be pivotally mounted up and down on the main drive shaft 73 using bearings 73a or 73b and driven simultaneously.

[0072] Figures 10a and 10b show the possibility of locking the tray 81, which is attached to the carrier 82 via a drive element (not visible) (e.g. as described in connection with Figures 6a / 6b and 9), in the housing or on a support structure 86 in the housing for the shaking process so that it cannot be temporarily pivoted about the main drive axis. The support structure 86 can be part of the housing or a separate component attached to the housing. To pivot the tray 81, the support 82 is pivotally mounted to the main drive shaft 83 via a bearing 83a (see, e.g., Figure 9).

[0073] FIG. 10b shows an enlarged view of section D of FIG. 10a. It comprises a first locking element 82a as a latch at or near its end away from the main drive shaft. As a counterpart of the first locking element 82a, a second locking element 82b is attached to the support structure 86. The first and second locking elements 82a and 82b are designed in particular to establish a detachable connection upon contact. As a result, the carrier 82 can be connected to the support structure 86 for the shaking process, in particular to prevent pivoting of the carrier 82 around the main drive shaft 83. Furthermore, part of the weight of the carrier 82 and the tray 81 together with the samples can be supported by the support structure 86, reducing the load on the bearing 83a on the main drive shaft.

[0074] Generally, the latching means comprises, for example, mechanical or magnetic components for releasably connecting the carrier 82 to the support structure 86. For example, the latching elements 82a and 82b may comprise magnets adapted to latch the carrier 82 to the support structure 86 by their mutual attractive force. Alternatively, the locking elements 82a and 82b may be designed as a snap lock or hinged lock in which the removable connection is generated mechanically.

[0075] Figures 11a, 11b and 11c show an embodiment of a shaker with divided trays, by means of which a particularly simple and reliable anti-rotation device for the trays can be realized. Figure 11a is a perspective view similar to Figure 1a, Figure 11b is a schematic cross-section of the shaker in the plane of the drive element similar to Figure 1b, and Figure 11c is a schematic vertical cross-section similar to Figure 6a. The features explained for the previous embodiment are equally applicable here.

[0076] The shaker comprises a housing 114 with a door 114a arranged to open and close the front of the housing. In Fig. 11a and Fig. 11b, the door 114a is shown in an open state. Furthermore, the shaker comprises a main drive shaft 113 which can be driven by a motor 115. A carrier 112 is rotatably mounted on the main drive shaft 113, which can be engaged with the housing, for example, by a latch mechanism (described above). A first drive element 116a and a second drive element 116b are then rotatably mounted on the carrier 112. The first drive element 116a is connected to the main drive shaft 113 via a first belt 118a and is driven by the first belt 118a. The second drive element 116b is connected to the first drive element 116a via a second belt 118b and is therefore also driven. It is important that the two drive elements 116a, 116b operate synchronously. For this reason, at least the second belt 118b is advantageously a toothed belt.

[0077] The first tray shaft 117a or the second tray shaft 117b is eccentrically journalled on or in the first drive element 116a or the second drive element 116b. The first tray part 111a or the second tray part 111b is attached, in particular non-rotatably attached, to the first tray shaft 117a or the second tray shaft 117b. Samples 119 can be placed on the tray parts 111a and 111b as described above, for example in test tubes or microtiter plates.

[0078] Here, a particularly simple and reliable anti-rotation device for the two tray parts 111a and 111b can be achieved by a flexible connection (not shown in Figures 11a-11c) between the two tray parts. Advantageously, this connection comprises a linear guide between the first tray part 111a and the second tray part 111b. The linear guide may, for example, be fixedly attached to one tray part while allowing the other tray part to slide along the guide. Such a flexible connection avoids, for example, damaging forces on the tray shaft and the bearings of the drive element, in particular as a result of thermal expansion of the carrier 112.

[0079] Alternatively, the device can also be provided with two drive elements 116a and 116b, as shown in Fig. 11a-11c, which are driven synchronously without a tray, as shown in the two tray parts 111a, 111b. In this case, the tray is formed in one piece and is journalled to the drive elements 116a, 116b via a first tray shaft 117a, 117b (as nevertheless shown in Fig. 11a-11c). In this case, the tray is also fixed against rotation, so that no additional guide elements, for example springs, are required, in particular between the tray and the housing 114. This contributes to achieving high speeds according to the invention.

[0080] It should be expressly noted that while preferred embodiments of the present invention are described in this application, the present invention is not limited thereto and may be embodied in other ways within the scope of the following claims.

Claims

1. 1. An apparatus for shaking a sample, comprising: - a carrier (62); a drive element (66) rotatably mounted on said carrier (62) around a drive axis and drivable by a drive (65); - a tray (61) arranged to be loaded with said samples (69); - a tray shaft (67) connected to said tray (61) and eccentrically mounted on said drive element (66); a counterweight (66a) attached to said drive element (66) and adapted to compensate for an imbalance caused during operation of said device by a given load on said tray (61); a center of gravity of the counterweight (66a) located on the opposite side of the tray shaft (67) with respect to the drive axis of the drive element (66); the center of gravity of the counterweight (66a) and the center of gravity of the tray (61), together with the tray shaft (67) and a predetermined load, lie in the same plane extending perpendicular to the drive shaft; a first torque exerted on said drive shaft by said tray (61) in conjunction with said tray shaft (67) and a predetermined load is equal in magnitude to and directed in an opposite direction to a second torque exerted on said drive shaft by said counterweight (66a), as said drive element (66) rotates about said drive shaft; The shaking frequency of the tray (61) by the drive (65) is at least 1000 rpm. Device.

2. the counterweight (66a) is adapted to compensate for both static and dynamic imbalance on the drive shaft; 2. The apparatus of claim 1.

3. the counterweight (66a) is the only counterweight on the drive element (66); In particular, there is no further counterweight on the side of the drive element (66) opposite the tray (61), 3. Apparatus according to claim 1 or 2.

4. The tray shaft (67) is attached to the center of the tray (61); 4. Apparatus according to any one of claims 1 to 3.

5. The tray (61) has a protrusion (61a) in the area of ​​the tray shaft (61), The counterweight (66a) is at least partially located within the protrusion (61a).

5. Apparatus according to any one of claims 1 to 4.

6. The counterweight (66a) has a mass of 0.1 to 1 kg; In particular, the counterweight (66a) is made of metal.

6. Apparatus according to any one of claims 1 to 5.

7. the eccentricity of the bearing of the tray shaft (67) on the drive element (66) is between 0.5 and 3 mm, in particular between 1 and 2 mm; 7. Apparatus according to any one of claims 1 to 6.

8. The frequency of shaking of the tray (61) by the drive (65) is at least 1500 rpm, in particular at least 2000 rpm or at least 2500 rpm; 8. Apparatus according to any one of claims 1 to 7.

9. The tray (61) is rectangular, In particular, said tray (61) has a length of 50 to 100 cm, and / or In particular, said tray (61) has a width of 30 to 70 cm, 9. Apparatus according to any one of claims 1 to 8.

10. The tray (61) is fixed against rotation relative to the carrier (62); 10. Apparatus according to any one of claims 1 to 9.

11. a second drive element rotatable about a second drive axis and journalled to said carrier (62) so as to be drivable by said drive (65), said second drive element being in particular connected to said drive element (66) via a toothed belt; a second tray shaft connected to said tray (61) and eccentrically journalled to said second drive element; a second counterweight attached to said second drive element, adapted to compensate for an imbalance caused during operation of said device by a given load on said tray (61); a center of gravity of the second counterweight is located on an opposite side of the second tray shaft with respect to the second drive shaft of the second drive element; the center of gravity of the second counterweight and the center of gravity of the tray (61) lie in the same plane, with the second tray shaft and a predetermined load, that extends perpendicular to the second drive shaft; a third torque exerted on the second drive shaft by the second tray shaft and the tray (61) together with a predetermined load when the second drive element rotates about the second drive shaft is equal in magnitude to and opposite in direction to a fourth torque exerted on the second drive shaft by the second counterweight; 11. The apparatus of claim 10.

12. the tray comprises a first tray portion (111a) and a second tray portion (111b); the first tray portion (111a) and the second tray portion (111b) are eccentrically journalled to a first drive element (116a) and a second drive element (116b) via a first tray shaft (117a) and a second tray shaft (117b) respectively connected to the first tray portion and the second tray portion, the first drive element (116a) and the second drive element (116b) are rotatably mounted on the carrier (112) and are drivable via a main drive shaft (113); the first tray part and the second tray part are connected to each other by a flexible connection, in particular by a linear guide.

11. The apparatus of claim 10.

13. said driving element (66) comprising a belt pulley for driving via a belt (68); 13. Apparatus according to any one of claims 1 to 12.

14. An openable housing (64) arranged to air-condition the interior of said housing (64), and wherein the tray (61), the tray shaft (67), the drive element (66), and the carrier (62) are located in the interior.

14. Apparatus according to any one of claims 1 to 13.

15. further comprising at least one further tray (41, 61) in said interior of the housing (44), in particular at least five further trays, together with further tray shafts, further drive elements, further counterweights and further carriers, said drive element (66) and said at least one further drive element being drivable via a main drive shaft (43, 63), 15. Apparatus according to any one of claims 1 to 14.

16. said drive (65) comprising a motor for driving said drive element (66) and, if present, said at least one further drive element, in particular via said main drive shaft (63), The motor is mounted externally to the housing (64); In particular, the interior of the housing (64) is thermally isolated from the motor.

16. Apparatus according to one of claims 14 or 15.

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